Fujioka T, Nomura K, Hasegawa M, Ishikura K, Kubo T
Department of Urology, Iwate Medical University School of Medicine, Morioka, Japan.
Br J Urol. 1994 Jan;73(1):23-31. doi: 10.1111/j.1464-410x.1994.tb07451.x.
To study the properties of lymphokine-activated killer (LAK) cells and the effect of immunotherapy with a combination of autologous LAK cells and interleukin-2 (IL-2) [LAK therapy] in 10 patients with metastatic renal cell carcinoma (RCC).
The LAK cells were generated from peripheral blood lymphocytes (PBL) by incubation in a serum-free medium (AIM-V) supplemented with IL-2 for 4 days and killer cells were administered intravenously twice a week. The LAK cells showed cytotoxicity against allogenic RCC cell lines and augmented NK and LAK activities. Their phenotypes were CD25+, HLA-DR+, CD3+, and CD16+. Furthermore, LAK cells released IFN-gamma, IL-1 beta, and TNF-alpha. The total number of LAK cells administered ranged from 3.8 x 10(9) to 52.6 x 10(9) cells and the total amount of IL-2 ranged from 150 x 10(5) to 900 x 10(5) U. The effect on pulmonary metastasis in response to LAK therapy was studied.
The outcome was complete response (1), partial response (1), minor response (2), no change (4) and disease progression (2). Toxic effects were transient and no serious side-effects occurred. Evaluation of host immune parameters indicated that a clinical response was expected in patients with increasing proportions of CD16+, CD25+, CD57+, HLA-DR+ and CD3+DR+ cells among PBL and with augmentation of NK and LAK activities. Brain metastases were detected in three patients during or after treatment.
LAK therapy appears to be effective in treating some patients with RCC and pulmonary metastasis. The potential for inducing brain metastasis, however, should be taken into account.
研究淋巴因子激活的杀伤（LAK）细胞的特性，以及10例转移性肾细胞癌（RCC）患者接受自体LAK细胞与白细胞介素-2（IL-2）联合免疫治疗[LAK治疗]的效果。
通过在补充有IL-2的无血清培养基（AIM-V）中孵育4天，从外周血淋巴细胞（PBL）中生成LAK细胞，并每周两次静脉注射杀伤细胞。LAK细胞对同种异体RCC细胞系表现出细胞毒性，并增强了NK和LAK活性。它们的表型为CD25 +、HLA-DR +、CD3 +和CD16 +。此外，LAK细胞释放IFN-γ、IL-1β和TNF-α。给予的LAK细胞总数为3.8×10⁹至52.6×10⁹个细胞，IL-2总量为150×10⁵至900×10⁵ U。研究了LAK治疗对肺转移的影响。
结果为完全缓解（1例）、部分缓解（1例）、轻度缓解（2例）、无变化（4例）和疾病进展（2例）。毒性作用是短暂性的，未发生严重副作用。对宿主免疫参数的评估表明，外周血淋巴细胞中CD16 +、CD25 +、CD57 +、HLA-DR +和CD3 + DR +细胞比例增加且NK和LAK活性增强的患者有望出现临床反应。治疗期间或治疗后在3例患者中检测到脑转移。
LAK治疗似乎对治疗一些RCC和肺转移患者有效。然而，应考虑到诱导脑转移的可能性。
